P E Vonk,J J Otten,H B E Elzinga,R J L van der Lans,G F J P Adriaensen,L B L Benoist,D R Hoven,W J Fokkens,S Reitsma,
BACKGROUNDDupilumab is effective in treating patients with type-2 dominant chronic rhinosinusitis with nasal polyps (T2-CRSwNP). Dosing starts at an interval of 1×/2 weeks (Q2W) with possible tapering upon disease control. Prolonging the interdose interval reduces patient burden and side effects and improves cost-effectiveness.OBJECTIVES(1) Analyze how many patients successfully reach and maintain extended tapering of at least 1×/12 weeks (Q12W), (2) evaluate differences in baseline characteristics and clinical measurements between patients who maintain disease control on ≥ Q12W ("super-responders") and patients who do not; (3) compare characteristics of "super-responders" to patients reaching Q12W but losing disease control on that dose ("excellent responders").METHODProspective cohort study including dupilumab-treated T2-CRSwNP patients with a minimum follow-up of 2.5 years.RESULTSFrom a total of 198 patients, 28 (14%) were "super-responders", and 26 (13%) "excellent responders." "super-responders" had less comorbid asthma (60.7% vs. 85.9%, p < 0.001), lower baseline immunoglobulin E levels (median [Q1: Q3]: 145 [58.7; 485] vs. 313 [135.5; 746]; p = 0.007) and a shorter time since last sinus surgery (2.5 years [1; 4.8] vs. 4 years [2; 7]; p = 0.026) compared to others. No differences were observed between "excellent" and "super-responders" at baseline, nor at the start of the Q12W interval. "excellent responders" showed worsening of clinical outcomes as well as increases in T2 markers in blood between start and stop of the Q12W interval.CONCLUSIONTapering of dupilumab to once every 12 weeks (Q12W) can be applied to super-responding patients. No clear predisposing factors were identified predicting the feasibility of extended tapering.
背景：dupilumab对2型显性慢性鼻窦炎伴鼻息肉（T2-CRSwNP）患者有效。给药间隔为1×/2周（Q2W），在疾病控制后可能逐渐减少。延长给药间隔可减少患者负担和副作用，并提高成本效益。(1)分析有多少患者成功达到并维持至少1×/12周（Q12W）的延长减量，(2)评估维持≥Q12W（“超级应答者”）疾病控制的患者与未达到Q12W的患者之间基线特征和临床测量的差异；(3)比较“超级应答者”与达到Q12W但在该剂量下失去疾病控制的患者（“优秀应答者”）的特征。方法前瞻性队列研究，纳入dupilumab治疗的T2-CRSwNP患者，随访时间至少为2.5年。结果198例患者中，“超级应答者”28例（14%），“优秀应答者”26例（13%）。“超级应答者”的共病哮喘较少（60.7% vs. 85.9%, p < 0.001），基线免疫球E水平较低（中位数[Q1: Q3]: 145 [58.7; 485] vs. 313 [135.5; 746]; p = 0.007），距上次鼻窦手术时间较短（2.5年[1.4.8]vs. 4年[2.7];p = 0.026）。在基线和Q12W间隔开始时，没有观察到“优秀”和“超级反应”之间的差异。“优秀应答者”表现出临床结果的恶化以及在Q12W间隔开始和停止期间血液中T2标记物的增加。结论dupilumab减量至每12周1次（Q12W）可用于超反应患者。没有明确的诱发因素预测延长锥形的可行性。
{"title":"\"Super-Responders\" to Dupilumab Treatment in Patients With Primary Diffuse Chronic Rhinosinusitis With Nasal Polyps.","authors":"P E Vonk,J J Otten,H B E Elzinga,R J L van der Lans,G F J P Adriaensen,L B L Benoist,D R Hoven,W J Fokkens,S Reitsma, ","doi":"10.1111/all.70151","DOIUrl":"https://doi.org/10.1111/all.70151","url":null,"abstract":"BACKGROUNDDupilumab is effective in treating patients with type-2 dominant chronic rhinosinusitis with nasal polyps (T2-CRSwNP). Dosing starts at an interval of 1×/2 weeks (Q2W) with possible tapering upon disease control. Prolonging the interdose interval reduces patient burden and side effects and improves cost-effectiveness.OBJECTIVES(1) Analyze how many patients successfully reach and maintain extended tapering of at least 1×/12 weeks (Q12W), (2) evaluate differences in baseline characteristics and clinical measurements between patients who maintain disease control on ≥ Q12W (\"super-responders\") and patients who do not; (3) compare characteristics of \"super-responders\" to patients reaching Q12W but losing disease control on that dose (\"excellent responders\").METHODProspective cohort study including dupilumab-treated T2-CRSwNP patients with a minimum follow-up of 2.5 years.RESULTSFrom a total of 198 patients, 28 (14%) were \"super-responders\", and 26 (13%) \"excellent responders.\" \"super-responders\" had less comorbid asthma (60.7% vs. 85.9%, p < 0.001), lower baseline immunoglobulin E levels (median [Q1: Q3]: 145 [58.7; 485] vs. 313 [135.5; 746]; p = 0.007) and a shorter time since last sinus surgery (2.5 years [1; 4.8] vs. 4 years [2; 7]; p = 0.026) compared to others. No differences were observed between \"excellent\" and \"super-responders\" at baseline, nor at the start of the Q12W interval. \"excellent responders\" showed worsening of clinical outcomes as well as increases in T2 markers in blood between start and stop of the Q12W interval.CONCLUSIONTapering of dupilumab to once every 12 weeks (Q12W) can be applied to super-responding patients. No clear predisposing factors were identified predicting the feasibility of extended tapering.","PeriodicalId":122,"journal":{"name":"Allergy","volume":"51 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2025-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145491741","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
María Salas,Alessandro Ghilarducci,Inmaculada Doña,Michele Schiappoli,Marina Labella,Annarita Dama,Elisa Olivieri,María José Torres,Patrizia Bonadonna
BACKGROUNDDiagnostic strategies for cephalosporin allergy are not well defined due to differences in inclusion criteria among studies and a lack of standardised diagnostic tests. Our aim was to describe the characteristics of patients with a suspicion of cephalosporin allergy and to analyse the role of in vivo tests.METHODSPatients with suspected cephalosporin allergy were prospectively evaluated (2019-2023). Diagnosis was achieved using clinical history, skin tests (STs) and, if negative, drug provocation tests (DPTs). A randomised group of patients who tolerated DPT were retested by STs at 2-8 weeks.RESULTS211 patients were evaluated, with 55.4% reporting IRs and 44.5% NIRs. Skin was involved in half of the patients reporting IRs and in all reporting NIRs (p < 0.0001). Anaphylaxis was experienced by 18% and shock by 7.1%. The cephalosporin most commonly involved was cefuroxime (63.6%) (p < 0.0001) in the Spanish cohort and cefazolin (51%) (p < 0.0001) in the Italian one. Allergy was confirmed in 57.2% of patients reporting IRs (47% by STs and 9.4% by DPT) and 14.9% of NIRs (5.3% by STs and 8.5% by DPT). In the positive-ST group, the percentage of grade II and III reactions was higher (p = 0.02) and the interval reaction-study shorter (p = 0.0007) than in negative-ST. Of the 48 patients retested, 1 (2.9%) who reported an IR and 1 (7.1%) who reported NIR resulted positive.CONCLUSIONSThe patterns of cephalosporin allergy may differ across different regions, being STs and DPT useful for diagnosis. Further studies are needed to confirm the role of retesting, as well as to identify which patients would benefit most from this procedure.
{"title":"Allergological Work-Up in Cephalosporin Allergy Diagnosis and Delabelling: The Experience From Two European Allergy Centres.","authors":"María Salas,Alessandro Ghilarducci,Inmaculada Doña,Michele Schiappoli,Marina Labella,Annarita Dama,Elisa Olivieri,María José Torres,Patrizia Bonadonna","doi":"10.1111/all.70120","DOIUrl":"https://doi.org/10.1111/all.70120","url":null,"abstract":"BACKGROUNDDiagnostic strategies for cephalosporin allergy are not well defined due to differences in inclusion criteria among studies and a lack of standardised diagnostic tests. Our aim was to describe the characteristics of patients with a suspicion of cephalosporin allergy and to analyse the role of in vivo tests.METHODSPatients with suspected cephalosporin allergy were prospectively evaluated (2019-2023). Diagnosis was achieved using clinical history, skin tests (STs) and, if negative, drug provocation tests (DPTs). A randomised group of patients who tolerated DPT were retested by STs at 2-8 weeks.RESULTS211 patients were evaluated, with 55.4% reporting IRs and 44.5% NIRs. Skin was involved in half of the patients reporting IRs and in all reporting NIRs (p < 0.0001). Anaphylaxis was experienced by 18% and shock by 7.1%. The cephalosporin most commonly involved was cefuroxime (63.6%) (p < 0.0001) in the Spanish cohort and cefazolin (51%) (p < 0.0001) in the Italian one. Allergy was confirmed in 57.2% of patients reporting IRs (47% by STs and 9.4% by DPT) and 14.9% of NIRs (5.3% by STs and 8.5% by DPT). In the positive-ST group, the percentage of grade II and III reactions was higher (p = 0.02) and the interval reaction-study shorter (p = 0.0007) than in negative-ST. Of the 48 patients retested, 1 (2.9%) who reported an IR and 1 (7.1%) who reported NIR resulted positive.CONCLUSIONSThe patterns of cephalosporin allergy may differ across different regions, being STs and DPT useful for diagnosis. Further studies are needed to confirm the role of retesting, as well as to identify which patients would benefit most from this procedure.","PeriodicalId":122,"journal":{"name":"Allergy","volume":"54 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2025-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145491745","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Kirandeep K. Gill, Carolina Moore, Onyekachi Nwogu, John W. Kroner, Wan‐Chi Chang, Jeffrey Burkle, Samuel J. Virolainen, Mariana L. Stevens, Asel Baatyrbek, Emily R. Miraldi, Jocelyn M. Biagini, Ashley L. Devonshire, Leah Kottyan, Justin T. Schwartz, Amal H. Assa'ad, Lisa J. Martin, Sandra Andorf, Gurjit K. Khurana Hershey, Krishna M. Roskin
IgE B cells produce antibodies responsible for the inappropriate specificity seen in allergic disease. In this study, we sequence antibody gene repertoires from a large, well‐characterized early life cohort at risk for developing food allergy. We found that food allergen sensitization was associated with lower IgE mutation frequencies that was abrogated in children living with a pet dog, suggesting potential molecular mechanisms underlying the hygiene hypothesis (i.e., protective effects of pet ownership and non‐antiseptic environs reported for allergic disease). We also observed increased IgE diversity and increased isotype‐switching to IgE, suggesting that B‐cell development is altered in those with food allergen sensitizations relative to those without. IgE diversity was even more extreme in subjects who were highly likely to be peanut allergic. Unlike food sensitization, we detected no effect of aeroallergen sensitization on IgE mutation levels and diversity. Consistent patterns of antibody rearrangement were associated with food allergen sensitization. These results have important implications for the allergic response driven by mast cells and basophils and the underlying drivers of the atopic march.
{"title":"B‐Cell Repertoire of Children With Atopic Dermatitis Exhibits Altered IgE Maturation Associated With Allergic Food Sensitization","authors":"Kirandeep K. Gill, Carolina Moore, Onyekachi Nwogu, John W. Kroner, Wan‐Chi Chang, Jeffrey Burkle, Samuel J. Virolainen, Mariana L. Stevens, Asel Baatyrbek, Emily R. Miraldi, Jocelyn M. Biagini, Ashley L. Devonshire, Leah Kottyan, Justin T. Schwartz, Amal H. Assa'ad, Lisa J. Martin, Sandra Andorf, Gurjit K. Khurana Hershey, Krishna M. Roskin","doi":"10.1111/all.70150","DOIUrl":"https://doi.org/10.1111/all.70150","url":null,"abstract":"IgE B cells produce antibodies responsible for the inappropriate specificity seen in allergic disease. In this study, we sequence antibody gene repertoires from a large, well‐characterized early life cohort at risk for developing food allergy. We found that food allergen sensitization was associated with lower IgE mutation frequencies that was abrogated in children living with a pet dog, suggesting potential molecular mechanisms underlying the hygiene hypothesis (i.e., protective effects of pet ownership and non‐antiseptic environs reported for allergic disease). We also observed increased IgE diversity and increased isotype‐switching to IgE, suggesting that B‐cell development is altered in those with food allergen sensitizations relative to those without. IgE diversity was even more extreme in subjects who were highly likely to be peanut allergic. Unlike food sensitization, we detected no effect of aeroallergen sensitization on IgE mutation levels and diversity. Consistent patterns of antibody rearrangement were associated with food allergen sensitization. These results have important implications for the allergic response driven by mast cells and basophils and the underlying drivers of the atopic march.","PeriodicalId":122,"journal":{"name":"Allergy","volume":"80 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2025-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145484664","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pauline J M Kuks,Tatiana Karp,Jorine E Hartman,Monica Kraft,Salman Siddiqui,Leonardo M Fabbri,Bianca Beghé,Klaus F Rabe,Alberto Papi,Christopher E Brightling,Dave Singh,Xingnan Li,Janwillem W H Kocks,Ulrica Scaffidi-Argentina,Huib A M Kerstjens,Irene H Heijink,Simon D Pouwels,Dirk-Jan Slebos,Maarten van den Berge
BACKGROUNDPrevious cluster analyses have identified subgroups of asthma. However, only a few studies included parameters of small airways dysfunction (SAD), or gene expression profiles reflecting underlying disease mechanisms. We aimed to identify clinically distinct asthma phenotypes, beyond GINA asthma severity, using available data from the ATLANTIS study which focused on identifying the prevalence of SAD in asthma and its role in asthma control, exacerbations and quality of life.METHODSThe ATLANTIS study included 773 asthma patients (mean age 44 years, 58% female, 76% never-smoker, GINA 1-5). Subjects were extensively characterized, including symptoms, parameters of large and small airways dysfunction, blood and sputum differential cell counts, and genome-wide gene expression profiling from nasal brushes. Clusters were generated using the Self-Organizing Map-Ward's method.RESULTSFour distinct clusters were identified: A (N = 62; 8%) characterized by the most frequent exacerbations, lower post-bronchodilator FEV1 % predicted, more small airways dysfunction, higher sputum and blood eosinophils, and high expression of asthma-related genes. B (N = 206; 27%) consisting of atopic patients with early-onset asthma, uncontrolled symptoms, and normal lung function and bronchial hyperresponsiveness, along with a high expression of asthma-related genes in the nasal epithelium. C (N = 277; 36%), predominantly male former smokers, with well-controlled asthma, mild obstructive lung disease, and relatively high neutrophil levels. D (N = 228; 29%), with normal lung function and low blood and sputum eosinophils.CONCLUSIONSFour distinct clusters were identified, where the presence of SAD was associated with high type-2 inflammation, lower lung function, and frequent exacerbations. SAD may be a marker of poorly controlled asthma and should be considered as an important clinical trait.
{"title":"Cluster Analysis to Identify Distinct Asthma Phenotypes in the ATLANTIS Cohort.","authors":"Pauline J M Kuks,Tatiana Karp,Jorine E Hartman,Monica Kraft,Salman Siddiqui,Leonardo M Fabbri,Bianca Beghé,Klaus F Rabe,Alberto Papi,Christopher E Brightling,Dave Singh,Xingnan Li,Janwillem W H Kocks,Ulrica Scaffidi-Argentina,Huib A M Kerstjens,Irene H Heijink,Simon D Pouwels,Dirk-Jan Slebos,Maarten van den Berge","doi":"10.1111/all.70127","DOIUrl":"https://doi.org/10.1111/all.70127","url":null,"abstract":"BACKGROUNDPrevious cluster analyses have identified subgroups of asthma. However, only a few studies included parameters of small airways dysfunction (SAD), or gene expression profiles reflecting underlying disease mechanisms. We aimed to identify clinically distinct asthma phenotypes, beyond GINA asthma severity, using available data from the ATLANTIS study which focused on identifying the prevalence of SAD in asthma and its role in asthma control, exacerbations and quality of life.METHODSThe ATLANTIS study included 773 asthma patients (mean age 44 years, 58% female, 76% never-smoker, GINA 1-5). Subjects were extensively characterized, including symptoms, parameters of large and small airways dysfunction, blood and sputum differential cell counts, and genome-wide gene expression profiling from nasal brushes. Clusters were generated using the Self-Organizing Map-Ward's method.RESULTSFour distinct clusters were identified: A (N = 62; 8%) characterized by the most frequent exacerbations, lower post-bronchodilator FEV1 % predicted, more small airways dysfunction, higher sputum and blood eosinophils, and high expression of asthma-related genes. B (N = 206; 27%) consisting of atopic patients with early-onset asthma, uncontrolled symptoms, and normal lung function and bronchial hyperresponsiveness, along with a high expression of asthma-related genes in the nasal epithelium. C (N = 277; 36%), predominantly male former smokers, with well-controlled asthma, mild obstructive lung disease, and relatively high neutrophil levels. D (N = 228; 29%), with normal lung function and low blood and sputum eosinophils.CONCLUSIONSFour distinct clusters were identified, where the presence of SAD was associated with high type-2 inflammation, lower lung function, and frequent exacerbations. SAD may be a marker of poorly controlled asthma and should be considered as an important clinical trait.","PeriodicalId":122,"journal":{"name":"Allergy","volume":"217 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2025-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145477496","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bjarke Hviid-Vyff,Søren Helbo Skaarup,Amber Duin,Johannes Martin Schmid,Hans Jürgen Hoffmann
{"title":"Low-Dose Intralymphatic Immunotherapy for Grass Pollen Allergy is Both Safe and Effective.","authors":"Bjarke Hviid-Vyff,Søren Helbo Skaarup,Amber Duin,Johannes Martin Schmid,Hans Jürgen Hoffmann","doi":"10.1111/all.70148","DOIUrl":"https://doi.org/10.1111/all.70148","url":null,"abstract":"","PeriodicalId":122,"journal":{"name":"Allergy","volume":"169 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2025-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145477441","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Correction to \"Deciphering Dysfunctional Regulatory T Cells in Atopic Dermatitis\".","authors":"","doi":"10.1111/all.70156","DOIUrl":"https://doi.org/10.1111/all.70156","url":null,"abstract":"","PeriodicalId":122,"journal":{"name":"Allergy","volume":"136 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2025-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145477453","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
James King, Ashley Woodcock, Antonio Anzueto, Alexander J. K. Wilkinson, Christer Janson, Richard Henderson, Sourabh Fulmali, Maximilian Plank
Background Rapid reductions in greenhouse gas (GHG) emissions are vital to combat climate change. Healthcare systems contribute ~5% of global GHG emissions, with pressurised metered‐dose inhalers (pMDIs) a significant contributor owing to their hydrofluorocarbon propellants. This study compared GHG emissions of a salbutamol pMDI using a low‐carbon propellant in clinical development, hydrofluoroalkane (HFA)‐152a, against current salbutamol inhalers. Methods Three ‘cradle‐to‐grave’ lifecycle analyses compared GHG emissions of salbutamol pMDIs with HFA‐152a and HFA‐134a, and salbutamol dry‐powder inhaler (DPI). Over 600 individual emission factors were calculated from > 2000 data points, and categorised into Active Pharmaceutical Ingredients Manufacture, Micronisation, Device, Formulation/Packaging, Use, Distribution and End‐of‐Life stages. 2023 manufacturing and supply data were collected from Algeria, Australia, Canada, France, Poland, Romania and Saudi Arabia. Carbon footprints were independently verified by the Carbon Trust. Results Mean total carbon footprint per salbutamol inhaler (based on 100‐year global warming potential [GWP100]) was 26.91, 2.06 and 0.69 kgCO 2 e for HFA‐134a pMDI, HFA‐152a pMDI and DPI, respectively. This equated to a 92% reduction in total emissions for HFA‐152a versus HFA‐134a. Most pMDI emissions came from the Use stage (HFA‐134a: 21.48 kgCO 2 e; HFA‐152a: 1.45 kgCO 2 e). Per actuation, emissions were 135, 10 and 11 gCO 2 e, respectively. For each pMDI, GHG emissions were similar across countries. Conclusions The low‐GWP propellant, HFA‐152a is expected to achieve > 90% reduction in the carbon footprint of salbutamol pMDI versus the currently used HFA‐134a. The development of salbutamol pMDI with HFA‐152a is a crucial step towards ensuring future patient access to salbutamol in a pMDI.
{"title":"Decarbonising Respiratory Care: The Impact of a Low‐Carbon Salbutamol Pressurised Metered‐Dose Inhalers","authors":"James King, Ashley Woodcock, Antonio Anzueto, Alexander J. K. Wilkinson, Christer Janson, Richard Henderson, Sourabh Fulmali, Maximilian Plank","doi":"10.1111/all.70141","DOIUrl":"https://doi.org/10.1111/all.70141","url":null,"abstract":"Background Rapid reductions in greenhouse gas (GHG) emissions are vital to combat climate change. Healthcare systems contribute ~5% of global GHG emissions, with pressurised metered‐dose inhalers (pMDIs) a significant contributor owing to their hydrofluorocarbon propellants. This study compared GHG emissions of a salbutamol pMDI using a low‐carbon propellant in clinical development, hydrofluoroalkane (HFA)‐152a, against current salbutamol inhalers. Methods Three ‘cradle‐to‐grave’ lifecycle analyses compared GHG emissions of salbutamol pMDIs with HFA‐152a and HFA‐134a, and salbutamol dry‐powder inhaler (DPI). Over 600 individual emission factors were calculated from > 2000 data points, and categorised into Active Pharmaceutical Ingredients Manufacture, Micronisation, Device, Formulation/Packaging, Use, Distribution and End‐of‐Life stages. 2023 manufacturing and supply data were collected from Algeria, Australia, Canada, France, Poland, Romania and Saudi Arabia. Carbon footprints were independently verified by the Carbon Trust. Results Mean total carbon footprint per salbutamol inhaler (based on 100‐year global warming potential [GWP100]) was 26.91, 2.06 and 0.69 kgCO <jats:sub>2</jats:sub> e for HFA‐134a pMDI, HFA‐152a pMDI and DPI, respectively. This equated to a 92% reduction in total emissions for HFA‐152a versus HFA‐134a. Most pMDI emissions came from the Use stage (HFA‐134a: 21.48 kgCO <jats:sub>2</jats:sub> e; HFA‐152a: 1.45 kgCO <jats:sub>2</jats:sub> e). Per actuation, emissions were 135, 10 and 11 gCO <jats:sub>2</jats:sub> e, respectively. For each pMDI, GHG emissions were similar across countries. Conclusions The low‐GWP propellant, HFA‐152a is expected to achieve > 90% reduction in the carbon footprint of salbutamol pMDI versus the currently used HFA‐134a. The development of salbutamol pMDI with HFA‐152a is a crucial step towards ensuring future patient access to salbutamol in a pMDI.","PeriodicalId":122,"journal":{"name":"Allergy","volume":"10 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2025-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145454712","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Rasmus K. Jensen, Michaela Miehe, Rosaria Gandini, Martin H. Jørgensen, Edzard Spillner, Gregers R. Andersen
Background IgE is the central driver of allergic responses. Prior studies have defined the conformation of the IgE Fc fragment bound to the FcεRIα ectodomain and the dynamic properties of the IgE Fc. It remains unknown, how these prior studies translate to the complex of a full antibody including the Fab arms with the receptor. Methods For structural analysis, crystallography, cryo‐EM and negative stain EM (ns‐EM) were combined. IgE variants were analyzed by mediator release and CD23 binding assays. Results An ensemble of 10 cryo‐EM structures of the full‐size IgE FcεRIα complex was obtained revealing that the receptor bound IgE adopts a pronounced T‐like conformation. Either Fab arm may rotate up to 40°. Two additional conformations with different arrangements of the Fab arms were captured in ns‐EM. The introduction of additional flexibility into the Fab‐Fc hinge does not compromise the biological activity of IgE, suggesting that the observed conformations of the IgE Fab‐Fc hinge exhibit equivalent biological function. Comparison of the full IgE receptor complex with recent cryo‐EM structures of the intact receptor reveals that FcεRI conformations differ markedly by the orientation of the ectodomain. Hence, our ensemble of IgE FcεRIα structures including the Fab arms enabled critical evaluation of FcεRI conformations. Conclusion Our data reveal the architecture of a full‐size IgE antibody bound to its receptor and a new layer of dynamics in FcεRIα bound IgE on top of the well‐established IgE Fc conformations. Development of novel anti‐IgE therapeutics may take into account these properties of FcεRIα bound IgE.
IgE是过敏反应的主要驱动因素。先前的研究已经确定了IgE Fc片段与Fcε ri α外畴结合的构象和IgE Fc的动态特性。目前尚不清楚，这些先前的研究如何转化为一个完整的抗体复合物，包括Fab臂与受体。方法采用晶体学、低温电镜和阴性染色电镜（ns - EM）相结合的方法进行结构分析。通过介质释放和CD23结合试验分析IgE变异。结果获得了全尺寸IgE FcεRIα复合物的10个低温电镜结构，表明受体结合的IgE具有明显的T - like构象。Fab臂可以旋转40°。在ns - EM中还捕获了另外两种具有不同排列方式的Fab臂构象。在Fab - Fc铰链中引入额外的柔韧性不会损害IgE的生物活性，这表明观察到的IgE Fab - Fc铰链的构象具有等效的生物功能。将完整的IgE受体复合物与最近完整受体的低温电镜结构进行比较，发现FcεRI构象在外畴的取向上有明显的不同。因此，我们的IgE FcεRIα结构集合（包括Fab臂）能够对FcεRI构象进行批判性评估。结论我们的数据揭示了一个与受体结合的全尺寸IgE抗体的结构，以及在已建立的IgE Fc构象之上的Fcε ri α结合IgE的新动态层。新型抗IgE药物的开发可能会考虑到FcεRIα结合IgE的这些特性。
{"title":"Cryo‐EM Structure of FcεRI Bound IgE Reveals Multiple Defined Conformations of the Fab‐Fc Hinge","authors":"Rasmus K. Jensen, Michaela Miehe, Rosaria Gandini, Martin H. Jørgensen, Edzard Spillner, Gregers R. Andersen","doi":"10.1111/all.70132","DOIUrl":"https://doi.org/10.1111/all.70132","url":null,"abstract":"Background IgE is the central driver of allergic responses. Prior studies have defined the conformation of the IgE Fc fragment bound to the FcεRIα ectodomain and the dynamic properties of the IgE Fc. It remains unknown, how these prior studies translate to the complex of a full antibody including the Fab arms with the receptor. Methods For structural analysis, crystallography, cryo‐EM and negative stain EM (ns‐EM) were combined. IgE variants were analyzed by mediator release and CD23 binding assays. Results An ensemble of 10 cryo‐EM structures of the full‐size IgE FcεRIα complex was obtained revealing that the receptor bound IgE adopts a pronounced T‐like conformation. Either Fab arm may rotate up to 40°. Two additional conformations with different arrangements of the Fab arms were captured in ns‐EM. The introduction of additional flexibility into the Fab‐Fc hinge does not compromise the biological activity of IgE, suggesting that the observed conformations of the IgE Fab‐Fc hinge exhibit equivalent biological function. Comparison of the full IgE receptor complex with recent cryo‐EM structures of the intact receptor reveals that FcεRI conformations differ markedly by the orientation of the ectodomain. Hence, our ensemble of IgE FcεRIα structures including the Fab arms enabled critical evaluation of FcεRI conformations. Conclusion Our data reveal the architecture of a full‐size IgE antibody bound to its receptor and a new layer of dynamics in FcεRIα bound IgE on top of the well‐established IgE Fc conformations. Development of novel anti‐IgE therapeutics may take into account these properties of FcεRIα bound IgE.","PeriodicalId":122,"journal":{"name":"Allergy","volume":"10 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2025-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145455317","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Supinda Bunyavanich, Mubeccel Akdis, M. Cecilia Berin, Alexander Eggel, Sarita U. Patil, Mohamed H. Shamji, Juan‐Felipe López, Hugh A. Sampson
The double‐blind placebo‐controlled oral food challenge (DBPCFC) has been the “gold standard” for diagnosing IgE‐mediated food allergy for the past 50 years. Despite tremendous strides in our understanding of basic mechanisms and clinical features of food allergy, we remain dependent on refinements of old technologies, i.e., skin tests and serum IgE measurements, to complement clinical history in making an accurate diagnosis of food allergies. However, recent technical advances in two effector cell assays, i.e., the basophil and mast cell activation tests, may soon bring these diagnostic biomarkers to the clinic. In addition, new advances in antibody assays, T‐cell assays, transcriptomics, and metabolomics in conjunction with machine learning and artificial intelligence may soon enable us to diagnose food allergy and accurately monitor immunotherapeutic outcomes without the need for an oral food challenge.
{"title":"Novel Biomarkers and Diagnostic Tools in Food Allergy","authors":"Supinda Bunyavanich, Mubeccel Akdis, M. Cecilia Berin, Alexander Eggel, Sarita U. Patil, Mohamed H. Shamji, Juan‐Felipe López, Hugh A. Sampson","doi":"10.1111/all.70133","DOIUrl":"https://doi.org/10.1111/all.70133","url":null,"abstract":"The double‐blind placebo‐controlled oral food challenge (DBPCFC) has been the “gold standard” for diagnosing IgE‐mediated food allergy for the past 50 years. Despite tremendous strides in our understanding of basic mechanisms and clinical features of food allergy, we remain dependent on refinements of old technologies, i.e., skin tests and serum IgE measurements, to complement clinical history in making an accurate diagnosis of food allergies. However, recent technical advances in two effector cell assays, i.e., the basophil and mast cell activation tests, may soon bring these diagnostic biomarkers to the clinic. In addition, new advances in antibody assays, T‐cell assays, transcriptomics, and metabolomics in conjunction with machine learning and artificial intelligence may soon enable us to diagnose food allergy and accurately monitor immunotherapeutic outcomes without the need for an oral food challenge.","PeriodicalId":122,"journal":{"name":"Allergy","volume":"168 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2025-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145447303","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Man Yui Chong,Weihong Shi,Maja Bulatović-Ćalasan,Rick Gert-Jan Pleijhuis,Ingrid Terreehorst,Philip H Li
{"title":"Improving Beta-Lactam Allergy Risk Stratification Through Digital Decision Support: A Randomized Crossover Study of BLAST-A.","authors":"Man Yui Chong,Weihong Shi,Maja Bulatović-Ćalasan,Rick Gert-Jan Pleijhuis,Ingrid Terreehorst,Philip H Li","doi":"10.1111/all.70147","DOIUrl":"https://doi.org/10.1111/all.70147","url":null,"abstract":"","PeriodicalId":122,"journal":{"name":"Allergy","volume":"86 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2025-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145440581","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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